|Year : 2021 | Volume
| Issue : 1 | Page : 86-89
Acute Intermittent Porphyria (AIP): A Difficult Diagnosis
Shailata Prisi, Parama Banerjee, Tarun Kumar Mishra
Department of Biochemistry, Maulana Azad Medical College, New Delhi, India
|Date of Submission||16-Nov-2020|
|Date of Decision||22-Jan-2021|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||28-Apr-2021|
Dr. Shailata Prisi
Department of Biochemistry, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi 110002
Source of Support: None, Conflict of Interest: None
Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder of heme biosynthesis but usually carry a good prognosis, if the condition is picked up early. Nonspecific nature of symptoms make it difficult to diagnose as a cause of acute neurovisceral attacks; thus demands high level of suspicion and early screening with necessary investigation to rule in the diagnosis. Here, we present a case of acute abdominal pain accompanied by weakness which rapidly progressed to seizure and quadriplegia and was associated with altered mental status. With the history of gastrointestinal symptoms correlating with presenting complaints was earlier misdiagnosed as Guillain–Barre syndrome. Later, MRI brain was suggestive of posterior reversible encephalopathy syndrome. On further evaluation, darkening of urine was observed leading to suspicion of AIP. Ehrlich test and Watson–Schwartz test was done which helped in coming to the right diagnosis and hence appropriate management.
Keywords: Acute intermittent porphyria, Ehrlich test, porphobilinogen, posterior reversible encephalopathy syndrome, Watson–Schwartz test
|How to cite this article:|
Prisi S, Banerjee P, Mishra TK. Acute Intermittent Porphyria (AIP): A Difficult Diagnosis. MAMC J Med Sci 2021;7:86-9
Key Messages: Acute intermittent porphyria (AIP) is a rare disorder of heme biosynthesis and is often misdiagnosed. Patients presenting with gastrointestinal symptoms and neurological disturbances should also be screened for AIP with simple biochemical urinary tests like Ehrlich test and Watson–Schwartz test. It should also be kept in mind that posterior reversible encephalopathy syndrome presenting as seizure is rarely associated with AIP as seen here. Thus, early diagnosis and prompt management will alleviate many long-term complications.
| Introduction|| |
Porphyria is a group of disorders due to deficiency of enzymes at different stages of heme synthesis. Acute intermittent porphyria (AIP) is a rare autosomal dominant disease resulting from deficiency of hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase which is the third enzyme of the heme biosynthesis pathway.
Clinical features of AIP develop due to accumulation of toxic intermediates like porphobilinogen (PBG) or delta-aminolevulinic acid (ALA). AIP has incidence of five per 100,000 people. As it shows low penetrance, even if mutation is present it will be rarely expressed. It most commonly presents with abdominal pain, hyponatremia, and urine discoloration., It can mimic many other diseases like Guillain–Barre syndrome (GBS) and psychosis.
Here we present a case of acute abdominal pain accompanied by weakness which rapidly progressed to quadriplegia and was associated with altered mental status.
| Case History|| |
A 16-year-old girl presented with an episode of acute abdominal pain with weakness, associated with constipation and vomiting. First episode of abdominal pain with cramps, bloody stool, and fever was 20 days back, precipitated by dehydration and fasting, which was severe in nature and lasted for 30 to 35 minutes. For the above complaints she got treated by her local practitioner. She had two similar episodes in the following week for which she got symptomatic treatment. After 3 days she had first episode of tonic seizure and was admitted to private hospital where she had another similar episode of seizure. Doctors noticed autonomic hyperactivity [i.e., raised blood pressure (BP) and tachycardia] and treated symptomatically. Her father noticed altered behavior like excessive and irrelevant talking. She developed ascending weakness involving all four limbs and trunk and got bed ridden within few hours. She also developed difficulty in breathing for last 2 days and was brought to our hospital.
On examination results were: pulse 140/min, BP 110/50 mm Hg, SpO2 93% on room air (R/A), and chest was bilaterally clear; both heart sounds were present with no added murmur. On examination abdomen was soft and non-tender (no organomegaly). Patient was conscious and oriented to time, place, and person. GCS score: E4V5M1 quadriparesis. Pupil bilaterally 5 mm. Mild bilateral lower facial weakness was observed with intact gag reflex. All reflexes were decreased except ankle reflex. On the basis of history and clinical findings patient was admitted with provisional diagnosis of GBS and treatment was planned accordingly.
After admission, patient was again investigated thoroughly. Blood investigations showed hyponatremia, hypomagnesemia, and altered liver enzyme levels [Table 1]. TRI-DOT tested negative. Later, radiological investigations were done [Table 2], magnetic resonance imaging (MRI) of brain [Figure 1] showed restricted diffusion on diffusion-weighted imaging which was suggestive of posterior reversible encephalopathy syndrome. Routine biochemical and microbiological examination of urine was normal. When standing darkening of urine sample was observed. Correlating the biochemical findings with history of intractable abdominal pain and deteriorating neurological condition, AIP was suspected. Spot urine was sent for analysis which tested positive for Ehrlich test and Watson–Schwartz test [Figure 2] and [Figure 3].
|Figure 1 MRI brain shows hyperintense areas in bilateral high parietal regions consistent with the diagnosis of PRES|
Click here to view
After diagnosis of AIP was established, she was treated symptomatically with levetiracetam and glucose infusion. Although AIP has autosomal dominant inheritance, no such family history was reported.
Patient responded to treatment and her condition gradually improved. She was discharged with necessary information regarding precipitating factors and medications. Six month follow-up was uneventful.
| Discussion|| |
Porphyrias are broadly classified as hepatic or erythropoietic types depending on which organ is mostly involved. AIP is hepatic type caused by HMBS deficiency. Expression of HMBS deficiency due to mutation is affected by many other factors (triggers), most frequent being missense mutations (46.3 %) of HMBS gene on chromosome 11.
Although 50% of HMBS activity is sufficient under normal conditions, its deficiency becomes evident when demand for heme increases in liver. Drugs (like alcohol, ketamine, etomidate, macrodantin, nifedipine, progesterone, and phenytoin), carbohydrate deprivation, smoking, and stress can act as trigger. Drugs like barbiturate induce cytochrome P450 derepressing heme synthesis. AIP has been more commonly reported in female of reproductive age group, which suggests role of sex hormones (may act as inducer) in clinical manifestation.,,
Our patient presented with intractable abdominal pain which is most common symptom of AIP, but its exact mechanism is still not established. If not suspected during early attacks, the condition of the patient deteriorates and neurological symptoms may develop. One explanation for neurological symptoms is accumulation of ALA which may affect normal gamma-aminobutyric acid (GABA) due to structural similarity. ALA may also disrupt blood–brain barrier causing reversible vasogenic edema mainly during hypertension, exceeding cerebral autoregulation limit, during acute attack of AIP. Repeated bouts of vomiting with decreased oral intake may be the cause of hyponatremia (most common electrolyte imbalance in AIP). Hypomagnesemia is also commonly seen in these patients. Both of them increase the risk of seizure. Motor symptoms are late to develop, which may progress to quadriplegia and respiratory distress.
Ehrlich test and Watson–Schwartz test for urine PBG are simple, quick, and useful as screening test for AIP. Equal volume of urine is mixed with equal amount of Ehrlich reagent. A red PBG–Ehrlich complex is formed which is characteristically insoluble in chloroform and N-butanol. On adding chloroform, PBG comes into the upper aqueous layer, giving it a red appearance, whereas urobilinogen–Ehrlich complex extracts into the chloroform layer. Large amount of PBG is excreted during acute attack giving positive Watson test. Quantification of PBG can be done with help of spectrophotometry of acidified urine which shows “Soret band” near 400 nm. Genetic workup will help identify the mutation in patient as well as family members at risk. As quantitative and molecular analysis were not available at our setting, our patient was provisonally diagnosed with AIP based on screening test and managed accordingly.
Mainstay of treatment of AIP is heme preparations which decrease level of ALA by negative feedback. However, this is not available in many developing countries where glucose infusion is standard treatment. Glucose exhibits inhibitory effect on ALA synthase and therefore alleviates the condition.
| Conclusion|| |
To conclude, AIP can have a variable presentation and can often be misdiagnosed. Therefore, patients presenting with gastrointestinal symptoms and neurological disturbances should also be screened for AIP. Ehrlich test is easy to perform and can help in early establishment of the diagnosis and management of the disease. This will also help in delaying many long-term complications of AIP (like chronic kidney insufficiency, hypertension, and hepatocellular carcinoma.
Authors thank Department of Radiodiagnosis for helping with interpretation of radiological investigations.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dajer A, Cooper L. Case report: acute intermittent porphyria. Emerg Med 2016;48:123-5.
Agarwal V, Singhal N. Porphyria: An uncommon cause of posterior reversible encephalopathy syndrome. J Pediatr Neurosci 2019;14:137-9.
] [Full text]
Swart G, Lim SS, Jude M. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome (PRES) and abdominal pain. Pract Neurol 2020;20(6):486-8.
Besur S, Schmeltzer P, Bonkovsky HL. Acute porphyrias. J Emerg Med 2015;49:305-12.
Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet 2015;8:201-14.
Soundravally R, Goswami K, Nandeesha H, Koner BC, Sethuraman KR. Acute intermittent porphyria: diagnosis per chance. Indian J Pathol Microbiol 2008;51:551.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]